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The Orphan Nuclear Receptor REV-ERBα Controls Circadian Transcription within the Positive Limb of the Mammalian Circadian Oscillator
Open accessAbstract
Mammalian circadian rhythms are generated by a feedback loop in which BMAL1 and CLOCK, players of the positive limb, activate transcription of the cryptochrome and period genes, components of the negative limb. Bmal1 and Per transcription cycles display nearly opposite phases and are thus governed by different mechanisms. Here, we identify the orphan nuclear receptor REV-ERBalpha as the major regulator of cyclic Bmal1 transcription. Circadian Rev-erbalpha expression is controlled by components of the general feedback loop. Thus, REV-ERBalpha constitutes a molecular link through which components of the negative limb drive antiphasic expression of components of the positive limb. While REV-ERBalpha influences the period length and affects the phase-shifting properties of the clock, it is not required for circadian rhythm generation.
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“The best characterized of these secondary loops involves the circadian transcription of the nuclear receptor Rev-erba (Nr1d1) by CLOCK-BMAL1 dimers acting through E-box regulatory elements; the resulting REVERBa/NR1D1 protein then inhibits Bmal1 transcription through retinoic acid-related orphan receptor response elements, resulting in circadian rhythms of Bmal1 mRNA expression (21).”
From Circadian rhythms, metabolism, and chrononutrition in rodents and humans (2016) · cites this paper as [21]
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Metadata
- Authors
- Preitner, N., Damiola, F., Luis-Lopez-Molina, Zakany, J., Duboule, D., Albrecht, U., & Schibler, U.
- Affiliations
- University of Geneva (CH)
- University of Fribourg (CH)
- Corresponding author
- Schibler, Ueli
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2002-07
- Volume
- 110
- Issue
- 2
- Pages
- 251-260
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2104290916
- Cited by
- 2,198
- References
- 49
- Citations by year
- 2026: 65 · 2025: 85 · 2024: 83 · 2023: 89 · 2022: 115 · 2021: 123 · 2020: 141 · 2019: 102 · 2018: 104 · 2017: 95 · 2016: 93 · 2015: 82 · 2014: 120 · 2013: 107 · 2012: 111
- FWCI
- 18.72
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Archive ouverte UNIGE (University of Geneva) (publishedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
- Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
- Archive ouverte UNIGE (University of Geneva) (submittedVersion, cc-by)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Light effects on plants
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Plant Molecular Biology Research
- Keywords
- NR1D1, orphan nuclear receptor, circadian clock, cryptochrome, period gene, phase shifting
- MeSH terms
- Animals, Base Sequence, Biological Clocks, Circadian Rhythm, DNA-Binding Proteins, Eye Proteins, Flavoproteins, Gene Expression Regulation, Heart, Humans, Liver, Mice, Inbred C57BL, Molecular Sequence Data, Nuclear Proteins, Promoter Regions, Genetic, Receptors, Thyroid Hormone, RNA, Messenger, Suprachiasmatic Nucleus, Transcription Factors, Transcription, Genetic, Trans-Activators, Photoreceptor Cells, Invertebrate, DNA, Complementary, Receptors, Cytoplasmic and Nuclear, Receptors, Retinoic Acid, Mice, Knockout, Cell Cycle Proteins, Response Elements, Drosophila Proteins, Receptors, G-Protein-Coupled, Mice, Rats, Basic Helix-Loop-Helix Proteins, CLOCK Proteins, ARNTL Transcription Factors, Cryptochromes, Period Circadian Proteins, Nuclear Receptor Subfamily 1, Group F, Member 1, Nuclear Receptor Subfamily 1, Group F, Member 3
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